Nearly three quarters of HIV-positive adults in a fourcity
US study had low levels of vitamin D, which is essential
for healthy bones and good general health.1
Blacks and Hispanics had a higher risk of vitamin D
deficiency than whites. Some risk factors for vitamin D
deficiency -- like hypertension and lack of exercise -- are
factors that HIV-positive people can change with their
doctors' help.

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Healthy vitamin D levels depend upon a good diet and
enough exposure to sun, which aids formation of vitamin
D in the body. Vitamin D deficiency may become
more common throughout the United States and other
countries, as people spend more time indoors and use
sunscreen outdoors.

Low vitamin D levels pose a threat to healthy bones and
may have a role in hypertension, heart disease, diabetes,
and cancer. All these diseases may develop more
often in people with HIV than in people without HIV.
And the risk of these diseases grows as HIV-positive
people live to older ages, thanks to antiretroviral therapy.
Vitamin D also contributes to a healthy immune
system, which is necessary to control HIV infection.

Recent smaller studies in the United States, the Netherlands,
and Switzerland found high rates of vitamin D
deficiency in people with HIV.2-4 SUN Study investigators
planned this research to confirm that finding in a
larger group of US people with HIV, to compare rates
of low D levels in people with and without HIV, and to
identify factors that may contribute to vitamin D deficiency
in people with HIV.

How the study worked. The SUN Study includes 700
HIV-positive men and women in Denver, Minneapolis,
Providence, and St. Louis. People signed up for this ongoing
study from March 2004 through June 2006. Everyone
gets regular checkups to track changes in their
health over time. When they entered the SUN Study,
participants had not taken antiretrovirals, or they had
begun treatment with at least three antiretrovirals and
were treated at a SUN study clinic.

After people entered SUN, health workers measured
their bone mineral density and levels of 25(OH)D, a
form of vitamin D that reflects vitamin acquired both
from sunlight and diet. No one assessed in the vitamin
D analysis took vitamin D supplements. The researchers
compared vitamin D levels in this HIV-positive
group and people in the general US population enrolled
in an ongoing study called the National Health
and Nutrition Examination Survey, or NHANES. For
this comparison, the researchers used NHANES data
from 2003-2004 and 2005-2006.

The SUN Study team defined vitamin D insufficiency
as a 25(OH)D level below 30 ng/mL (nanograms per
milliliter), and they defined vitamin D deficiency as a
25(OH)D level below 20 ng/mL. The researchers used
standard statistical methods to identify factors associated
with vitamin D deficiency or insufficiency, regardless
of what other risk factors a person might have.

What the study found. The HIV-positive study
group included 672 people, 76% of them men, 58%
white, 30% black, 10% Hispanic, and the rest of another
race or ethnic group. Median age stood at 41
years, and median CD4 count was 471. While 79% of
the HIV group were taking antiretrovirals, 74% had a
viral load below 400 copies. The general-population
NHANES group represented nearly 170 million US
adults, 51% of them men, 70% of them white, with a
median age of 43 years.

In a statistical analysis that accounted for the impact of
age, race, and gender, 30% of the HIV-positive group
and 39% of the general-population group had vitamin
D deficiency. The rate of vitamin D insufficiency was
also lower in the HIV group -- 70% versus 79% in the
general-population group. In both the HIV group and
the general-population group, low vitamin D levels
were more common in blacks and Hispanics (compared
with whites) and in people with lower exposure to sunlight.
In the HIV group, a higher proportion of women
than men had low D levels (80% versus 69%). But female
gender was not independently associated with low
vitamin D in the statistical analysis described below.

The statistical analysis to identify independent predictors
of vitamin D deficiency considered the impact of
(1) basic personal and behavioral factors such as age,
gender, race, and exercise, (2) HIV-related factors such
as CD4 count, viral load, and antiretrovirals taken, (3)
environmental factors such as sunlight exposure and
month of blood collection to measure vitamin D, and
(4) clinical factors such as weight, bone mineral density,
various diseases, and non-HIV drugs.

Figure 1. Several factors independently raised
or lowered the risk of low vitamin D levels in a
study of 672 HIV-positive adults in the United
States. More sunlight means above the median
monthly average ultraviolet light exposure.
BMI means body mass index, calculated as kilograms
per height in meters squared. No exercise
means no exercise versus exercising 3 or
more days a week.

This analysis showed that blacks, Hispanics, heavier people,
people with hypertension, and a few other groups
had a higher risk of low vitamin D levels (Figures 1 and
2). Notably, people who did not exercise had more than
a 3 times higher risk of low vitamin D than people who
exercised 3 or more times a week (Figure 1).

People taking Sustiva (efavirenz) had a higher risk of
low vitamin D. In contrast, people taking Viread (tenofovir)
or Norvir (ritonavir) had a lower risk of low
vitamin D (Figure 2). Viread is part of the combination
drugs Truvada and Atripla. Norvir is used to boost other
protease inhibitors, such as Prezista (darunavir) and
Reyataz (atazanavir). In a separate analysis, longer time
taking a Sustiva-containing combination raised the risk
of low vitamin D levels.

Factors that did not affect risk of low vitamin D included
age, gender, time since HIV diagnosis, initial CD4
count, lowest-ever CD4 count, having an AIDS disease,
having hepatitis B or C infection, having diabetes, taking
a nucleoside (such as Emtriva, Epivir, or Ziagen),
and taking Viramune (nevirapine).

What the results mean for you. This study found that a
large group of HIV-positive people in the United States
had a slightly lower rate of low vitamin D levels than
people in the general US population. Still, almost three
quarters of the HIV group had moderately low or severely
low vitamin D concentrations. Too little vitamin
D from diet and sunlight poses a threat to people with
HIV because vitamin D is essential for healthy bones
and HIV-positive people have a high risk of bone disease. Vitamin D probably also contributes to a healthy
immune system, which is critical for people with HIV
because HIV attacks the immune system.

This study also identifies risk factors for low vitamin D
in people with HIV (Figures 1 and 2). Anyone with HIV
can avoid or reverse some of these risk factors, including:

High weight

Lack of exercise

Low sun exposure

Hypertension

Using a strong sunscreen can help prevent skin cancer
by blocking ultraviolet light from the sun. However, ultraviolet
light helps the body form vitamin D. A healthy
balance between too much sunlight and too little sunlight
is hard to define. But it's probably safe to say that
people who live in northern regions (where yearly sun
exposure is lower) and people who spend lots of time
indoors should consider outdoor activity (including
exercise) on sunny days. The National Institutes of
Health notes one recommendation of "approximately
5 to 30 minutes of sun between 10 AM and 3 PM at
least twice a week to the face, arms, legs, or back without
sunscreen [or] moderate use of commercial tanning
beds that emit 2% to 6% ultraviolet B radiation."5 Few
foods contain high levels of vitamin D.5 Fatty fish, such
as salmon, tuna, and mackerel -- along with cod liver
oil -- are the best sources. Smaller amounts of vitamin D
can be found in beef liver, cheese, and eggs.

This study found a link between taking Sustiva and low
vitamin D, while taking Viread or Norvir was linked to
higher vitamin D levels. Sustiva may lead to lower vitamin
D by altering vitamin D processing in body. Alcohol
and some anti-epilepsy drugs may lower vitamin D
levels the same way. Anti-epilepsy drugs did not affect
vitamin D levels in this study, and the researchers could
not assess the potential impact of alcohol. In contrast,
Norvir may alter vitamin D processing in the body in
a way that yields higher levels. Viread may promote
higher vitamin D levels by impairing kidney function
(but of course impaired kidneys are not desirable).

Whether everyone with HIV should be tested for vitamin
D levels remains unknown (although the authors
of this study do recommend testing). Research has not
shown that people with low vitamin D levels improve
their health by taking vitamin D supplements. The National
Institutes of Health does say that people "with
limited sun exposure need to include good sources of
vitamin D in their diet or take a supplement to achieve
recommended levels of intake."

A committee apointed by the Institute of Medicine recommends
400 IU of vitamin D daily as the estimated
average requirement, 600 IU daily as the recommended
dietary allowance, and 4000 IU daily as the upper
level intake for everyone from 9 to 70 years old, including
pregnant and lactating women.6 But neither this
committee nor the National Institutes of Health5 offers
special advice for people with HIV. The National Institutes
of Health does list some groups with a high risk of
low vitamin D levels:5

Older people

People with limited sun exposure

People with dark skin

People with fat absorption problems

People who are obese or have had gastric
bypass surgery

HIV-positive people with these risk factors for low D
levels -- or the risk factors found in this study -- should
talk to their doctors about whether their vitamin D level
should be measured and what steps they might take to
raise low levels.

References

Dao CN, Patel P, Overton ET, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D
levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population.
Clin Infect Dis. 2011;52:396-405.

This article was provided by The Center for AIDS. It is a part of the publication HIV Treatment ALERTS!.
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